title: Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar-Kyoto and spontaneously hypertensive rats.
abstract: BACKGROUND
  Calcium entry through nifedipine-sensitive L-type voltage-dependent calcium channels (L-VDCC) is augmented in spontaneously hypertensive rats (SHR) characterized by enhanced sympathetic vasoconstriction. However, the changes of calcium sensitization mediated by RhoA/Rho kinase pathway are less understood.
  
  
  RESULTS
  The participation of calcium entry and calcium sensitization in the control of blood pressure (BP) and vascular contraction was studied in SHR and normotensive Wistar-Kyoto (WKY) rats. The acute administration of fasudil (Rho kinase inhibitor) caused BP decrease which lasted longer in SHR. Fasudil also attenuated adrenergic contraction in femoral or mesenteric arteries of WKY and SHR. BP reduction elicited by fasudil in WKY was more pronounced than that induced by L-VDCC blocker nifedipine (-33±2 vs. -15±3% of baseline BP, P<0.001), whereas both inhibitors were similarly effective in SHR (-36±4 vs. -41±2%). Fasudil pretreatment also attenuated BP elevation elicited by L-VDCC agonist BAY K8644 more in WKY than in SHR (-63±4 vs. -42±5%, P<0.001), indicating reduced calcium sensitization in SHR. Moreover, fasudil pretreatment shifted norepinephrine dose-response curves to the right more in WKY than in SHR. The additional nifedipine pretreatment shifted these curves further to the right but this shift was more pronounced in SHR than in WKY. Thus adrenergic vasoconstriction is more dependent on L-VDCC in SHR and on RhoA/Rho kinase pathway in WKY rats.
  
  
  CONCLUSIONS
  Ca sensitization mediated by RhoA/Rho kinase pathway is attenuated in SHR compared with normotensive WKY rats. This might be a part of the compensation for enhanced Ca entry through L-VDCC in genetic hypertension.
authors.affiliation: aInstitute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic bInstitute of Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovakia *Michal Behuliak and Mária Pintérová contributed equally to the writing of this article.
authors.forename: Michal
authors.initials: M
authors.lastname: Behuliak
authors.forename: Mária
authors.initials: M
authors.lastname: Pintérová
authors.forename: Michal
authors.initials: M
authors.lastname: Bencze
authors.forename: Miriam
authors.initials: M
authors.lastname: Petrová
authors.forename: Silvia
authors.initials: S
authors.lastname: Líšková
authors.forename: Petr
authors.initials: P
authors.lastname: Karen
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kuneš
authors.forename: Ivana
authors.initials: I
authors.lastname: Vaněčková
authors.forename: Josef
authors.initials: J
authors.lastname: Zicha
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011941:Receptors, Adrenergic / Q000378:metabolism; D013696:Temperature; D014661:Vasoconstriction / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D011941:Receptors, Adrenergic; D009569:Nitric Oxide; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D009543:Nifedipine; C049347:fasudil; D002118:Calcium; D009638:Norepinephrine